Advanced pharmaceutical bulletin最新文献

Purpose: Breast cancer is the leading cause of cancer-related deaths among women. Chemotherapy faces challenges such as systemic toxicity and multidrug resistance. Advances in nanotechnology have led researchers to develop safer and more efficient cancer treatment methods.

Methods: The thin-film hydration method was employed to synthesize PEGylated nanoliposomes (NLs) loaded with raloxifene (RLX) and a combination of RLX and rutin. The NLs were characterized using a Zetasizer® instrument, transmission electron microscopy (TEM), and high-performance liquid chromatography (HPLC) analysis. The encapsulation of RLX and rutin was confirmed, and cell viability assays were conducted against breast cancer and normal endothelial cell lines.

Results: The encapsulation efficiency significantly increased in the mixed formulation, with RLX reaching 91.28% and rutin 78.12%, indicating successful encapsulation. These NLs remained stable for up to two months at room temperature and one month at 4°C, demonstrating a biphasic release pattern. After 24 hours, approximately 17% of RLX was released from the NLs and 25% from the mixed NLs. In contrast, 55% of rutin was released from the NLs and 70.4% from the mixed NLs within 72 hours. The inclusion of rutin or RLX in the liposomal formulation reduced cytotoxicity against breast cancer cell lines, as indicated by the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. However, it improved safety in normal human cells and tissues.

Conclusion: PEGylated NLs loaded with RLX and rutin demonstrated safe anti-breast cancer effects, outperforming mixed NLs, suggesting the potential for a safer and more targeted treatment. Further investigations are needed into clinical translation.

Purpose: Tumor hypoxia is a key barrier to successful delivery and activity of anti-cancer agents. To tackle this, we designed hypoxia-responsive Au-PEI-Azo-mPEG nanoparticles (NPs) denoted as APAP NPs for targeted delivery of hypoxia-activated prodrug (HAP), tirapazamine (TPZ) to hypoxic breast cancer cells.

Methods: AuNPs were first synthesized. And then, were coated with polyethylene imine (PEI) by EDC-NHS chemistry. To realize NP biocompatibility and self-activating potential, a hypoxia-cleavable mPEG-AZO linker shell was coupled to the Au-PEI core. The hypoxia-responsible behavior of nanoparticles was analyzed under 21% O₂ (normoxia) and 1% O₂ (hypoxia) condition in 2D cell culture as well as MDA-MB-231 and MCF-7 spheroids as reliable biomimetics of tumor hypoxia.

Results: APAP NPs elicited comparable cytotoxicity upon MDA-MB-231 cancer cells lowering TPZ IC₅₀ to 7.46 µg/mL after 24 h. And were capable of enhanced ROS generation (P<0.001), and reduced mitochondrial membrane potential under hypoxia condition compared to the control (P<0.0001). Further, these NPs induced widespread apoptosis in both 2D and 3D cancer cell culture (P<0.0001), significantly reduced cell adhesion density (P<0.01), increased cell uptake by ~100 folds under hypoxia condition, and destroyed large MCF-7 spheroids by 72 h.

Conclusion: Together, APAP@TPZ as biocompatible, and multi-stage activating platforms afford deepened penetration of HAP to hypoxic tumor core, where PEG detachment and TPZ bioreduction into its active form promote selective and effective eradication of hypoxic breast cancer microtumors.

Purpose: Myocardial infarction (MI), the leading cause of human mortality, is induced by a sudden interruption of blood supply. Among various stem cell types, endothelial progenitor cells (EPCs) are novel and valid cell sources for the restoration of vascularization in the ischemic tissue. The present study aimed to evaluate the regenerative properties of EPCs in rodent models of MI.

Methods: A comprehensive systematic search was implemented in Cochrane Library, Embase, PubMed, Scopus, and Web of Science databases without language limitation in Sep 2024. Of the 67 papers pooled, 42 met the inclusion criteria and were subjected to multiple analyses.

Results: Compared to the MI group, the overall effect size was confirmed in the groups receiving EPC with enhanced angiogenesis (SMD: 2.02, CI 95%: 1.51-2.54, P<0.00001; I²: 82%), reduced fibrosis (SMD: -1.48; 95% CI-2.15, -0.81; P<0.0001; I²: 88%), improved ejection fraction (EF; SMD: 1.72; 95% CI-1.21, 2.23; P<0.00001; I²: 87%), and fractional shortening (FS; SMD: 1.58; 95% CI-1.13, 2.03; P<0.00001; I²: 82%). Data confirmed significant improvements in the cardiac tissue parameters after intramyocardial injection of EPCs.

Conclusion: These data showed that EPC transplantation is an alternative therapy to ameliorate ischemic myocardium in rodents via the stimulation of angiogenesis, reduction of fibrosis, and improvement of fractional shortening and ejection fraction.

Purpose: Calumenin (CALU) is a calcium-binding protein involved in several physiological processes, exhibiting tumor-specific expression variation and emerging as a potential player in cancer progression. This study aimed to investigate the correlation between CALU and clinicopathological features in breast cancer (BC) and perform a functional assessment of CALU based on a microRNA-mediated knockdown approach.

Methods: The BC tissues' CALU expression was measured by q-RT-PCR. We looked at correlations between changes in CALU expression and clinicopathological characteristics. We adopted a CALU knockdown approach using an artificial microRNA (amiR), expressed through an episomal vector, in BC cell lines. Epithelial to mesenchymal transition (EMT) markers were then assessed, and cell cycle, migration, proliferation, and apoptosis were analyzed.

Results: When compared to the normal surrounding tissues, the BC tissues showed a 3.4-fold increase in CALU expression. This was significantly correlated with clinicopathological parameters such as histological grade, Ki-67 expression, TNM stage, lymph node involvement, and vascular lymph invasion. Key EMT markers, including GSC, MMP2, TIMP1, TGF1, SLUG, ZEB1, ZEB2, SNALI1, and TWIST1, were downregulated as a result of CALU knockdown, which prevented cell migration and proliferation and caused cell cycle arrest and apoptosis in the BC cell lines.

Conclusion: The results of the amiR-mediated knockdown approach support the findings that CALU is a potential promoter of BC, as evidenced by the upregulation of CALU in BC tissues and its correlation with clinicopathological features, which highlights its role in BC progression.

Purpose: The present study aimed to fabricate microneedles (MNs) for transdermal delivery of insulin. Chitosan-conjugated carboxy phenyl boronic acid polymer was synthesized and characterized to load insulin in the form of nanoparticles.

Methods: Optimized insulin nanoparticles (ILN-NPs) were loaded into MN arrays by micromolding, and the resulting MN patches were characterized by scanning electron microscopy (SEM) and mechanical failure tests. The MNs were evaluated for skin insertion via a confocal laser scanning microscope. The in vivo efficacy (blood glucose levels [BGLs] and serum insulin concentration) of the MNs was studied in diabetic rats in comparison with traditional subcutaneous insulin injection.

Results: In diabetic rats treated with MNs incorporated with insulin-loaded nanoparticles (ILN-MNs), the BGLs reached≤200 mg/dL at 2 h following the application of the ILN-MNs and maintained BGLs≤200 mg/dL from 2-8 h. The BGLs decreased to 29 mg/dL at 2 h following the subcutaneous administration of insulin. After 6 h, the BGLs rose to their initial level. These results were supported by the corresponding serum insulin concentrations.

Conclusion: The findings of this study demonstrate the reliability of the developed ILN-MNs for sustaining normal BGLs in diabetic rats. Therefore, it can be further explored as an approach for diabetes treatment to improve patient outcomes and quality of life.

Purpose: This study aims to analyze the technological impact of papers that Advanced Pharmaceutical Bulletin (APB) has published through patent-to-paper citations analysis.

Methods: Current research uses a Scientometric approach to analyze patent citations to published papers by the APB. The Lens has been used for collecting patents that cited related papers. Some of the data analysis was conducted using the Lens analytical tool.

Results: Results show that APB's patent-to-paper citation rate is 32.39%, above the toxicology field average (6.15%) but below pharmacology (46.33%), indicating significant technological influence. APB contributes to both science and technology, attracting global inventors.

Conclusion: The patent citations metric can be used to understand how a journal contributes to technological progress. However, these methods need to be standardized and promoted to understand a journal's real value in technology contribution.

Purpose: This study explores the potential of generative AI models to aid experts in developing scripts for pharmacokinetic (PK) models, with a focus on constructing a two-compartment population PK model using data from Hosseini et al.

Methods: Generative AI tools ChatGPT v3.5, Gemini v2.0 Flash and Microsoft Copilot free could help PK professionals- even those without programming experience-learn the programming languages and skills needed for PK modeling. To evaluate these free AI tools, PK models were created in R Studio, covering key tasks in pharmacometrics and clinical pharmacology, including model descriptions, input requirements, results, and code generation, with a focus on reproducibility.

Results: ChatGPT demonstrated superior performance compared to Copilot and Gemini, highlighting strong foundational knowledge, advanced concepts, and practical skills, including PK code structure and syntax. Validation indicated high accuracy in estimated and simulated plots, with minimal differences in clearance (Cl) and volume of distribution (V c and V p) compared to reference values. The metrics showed absolute fractional error (AFE), absolute average fractional error (AAFE), and mean percentage error (MPE) values of 0.99, 1.14, and -1.85, respectively.

Conclusion: These results show that generative AI can effectively extract PK data from literature, build population PK models in R, and create interactive Shiny apps for visualization, with expert support.

Treatment of glioblastoma multiforme (GBM) has been a great challenge before medical fraternity since last century owing to a median survival of less than 15 months, despite of intensive therapy. Neurosurgeries, intense chemotherapy, advanced radiotherapy, and targeted therapies have bought some extension to the life of GBM patients. Combination and targeted therapies could bring a concrete approach to tackle the complexities of GBM treatment. Monoclonal antibodies (mAbs) have already proved their potential, owing to their high affinity and target-specificity, as a promising cancer immunotherapy. In addition, the unique optical properties of quantum dots (QDs) make them an ideal choice of nanocarrier for delivering the chemotherapeutic agents across the blood-brain barrier (BBB) and blood-tumor barrier (BTB). Present review is a concise compilation of the investigations on mAbs conjugation on the QDs surface and their anticancer efficacy against GBM. The core purpose of this review is to discuss the major challenges in the current treatment of GBM and how the mAbs-conjugated QDs have enhanced the therapeutic efficacy in the targeted immunotherapy of GBM tumor. At the end of the article, authors have briefed about the current clinical status of mAbs in GBM treatment, which would urge the researchers to explore them in conjugation with the QDs-based delivery systems. Advancements in this strategy could further open the potential avenues in the future treatments of GBM.

One of the major reason of deaths due to cancer globally is caused by lung cancer of which the two main types include non-small cell and small cell lung cancer. The onset of treatment-resistance in cancer cells offers a serious obstacle to the therapeutic effect despite that primary conventional treatments have provided significant benefits and cures. Cancer immunotherapy offers a compelling alternative in patients by utilizing their immune system to enhance its ability to fight against tumors. Cancer immunotherapy includes treatment with cytokines, hormones, bacterial products, monoclonal antibodies, vaccines, etc. Many of these immunotherapies are clinically tested in lung cancer patients. Tumor-associated antigens specific for lung cancer are being targeted using monoclonal antibodies and vaccines. Genetically engineered T-cells that are cultured outside the body are reinfused into the patients. In this review, we describe the different immunotherapeutic approaches that have been clinically tested and used to treat lung cancer globally. The data presented are collected from published studies through electronic databases like Google Scholar and Pubmed using keywords like immunotherapy, adoptive cell therapy, cancer, vaccines, lung cancer and immunological checkpoint inhibitors. The clinical trial results were acquired from ClinicalTrials.gov.in, a database of clinical research studies and their result updates. The review examines the current immunotherapies available for lung cancer treatment globally. While these therapies offer significant benefits to the community, several challenges have hindered their widespread adoption. Key issues such as adverse effects, high costs and varying patient responses to lung cancer immunotherapy require careful consideration. The integration of advanced technologies, including artificial intelligence and bioinformatics tools, along with combinatorial strategies and thorough monitoring, has the potential to increase widely use of lung cancer immunotherapy.